Substrate analog fructokinase inhibitors will be used to study mammalian fructose metabolism with particular emphasis as to their effects on fructose utilization in the liver. Fructose analogs will be synthesized and characterized. The suitabilities of these compounds to serve as substrates and inhibitors for the enzymes of mammalian fructose metabolism, particularly fructokinase, will be evaluated. Analogs will also be tested as to their inhibition of fructose metabolism in liver in vitro. Derivatives which show antimetabolic potential in these experiments will be further studied as to their effects in vivo. Their toxicity will be evaluated and they will be monitored for their influence on fructose metabolism when administered to mice. In these experiments excretion of fructose and the accumulation of metabolites in tissues and body fluids will be measured. Their efficacy in producing an animal model of essential fructosuria will be evaluated. Fructokinase inhibitors will further be used to evaluate the potentialities of fructose utilization by peripheral tissues in normal and diabetic animals.